Jared Weiss, MD, Oncologist at UNC Lineberger Comprehensive Cancer Center, and Wendell Yarborough, MD, MMHC Head & Neck Surgeon at UNC Hospitals talk about treating tongue cancer.
Interview conducted by Ivanhoe Broadcast News in 2024.
When you think about cancers, do you think all of them are bad? Getting cancer on your tongue is pretty frightening because it can affect a lot of things that you do, can really affect your lifestyle. You’ve seen that, right?
Weiss: Yeah, the two reasons that we treat cancer in general, both when it is curable and actually also when it is not, are that we want our patients to live for a long time and we want to preserve their quality of life. Survival is pretty simple. It’s an easy measure, we all understand that. But quality of life, I would argue, is both more important and more complicated. It’s very multi-factorial. But even if we narrow in on physical quality of life, or perhaps even more narrowly cancer related physical quality of life, there are multiple dimensions impacting that. The two dominant ones are the side effects of the therapy, and the cancer itself, the awful things that cancer can do. And if we want to maximize the quality of life of our patients, we can never ignore either of these. When we think specifically about head and neck cancer, and we think even more narrowly specifically about tongue cancer, these aren’t necessarily the side effects that people think of every day. I think, when you think about cancer therapy, people think about nausea, vomiting, fatigue, all of that is very real. But when you come to an anatomic site like the tongue, you’re talking about problems that are not just during the treatment, but that can affect the person for the remainder of their life. So for example, when we do chemo radiation, you have a six, seven week course and it can take months to recover after that. That can be awful. Let’s not minimize that in any way, but when you talk about a curable patient, a patient who has cured you have side effects that may last them the rest of their life, which is now decades. And so you’re talking about very long-term quality of life concerns. And when you think about the tongue in particular, it is important for speech, and it’s really important for swallowing, and obviously for taste. But the swallowing function cannot be underestimated in addition to the things we obviously think of. If your tongue doesn’t work right, you aspirate, meaning that the food goes down, or even secretions, your own saliva can go down the wrong way. People can get serial pneumonia that can also be big hit to quality of life. And so when we see patients here at UNC for a disease like tongue cancer that has these characteristics, we all get together in our multidisciplinary tumor board that has the medical oncologist, the radiation oncologists, the surgical pathologists, the speech pathologists, the dentists, the nurse navigators. I’m probably leaving off half the people involved. But this massive team of people who care deeply about the quality of life of patients. And that’s what our conversation often centers around. How can we cure this person? Yes. But also how can we preserve their short, and even more importantly, long-term quality of life as much as possible.
That’s where your clinical trial comes into play, correct?
Weiss: Yeah. So most clinical trials for head and neck cancer either try to increase the cure rate by dialing up the intensity of the therapy at the cost of more side effects. Or for better prognosis cancers, try to dial down the intensity of the therapy to reduce the side effects with the risk of reducing the cure rate. We’ve done now two trials in the operative setting where we’ve tried to do serial therapy with, at each stage, an adjustment of the intensity of the neck stage based on what’s actually required. And so in our standard approach, we do surgery, and then the risk factors on the surgical pathology report drive what comes next. If anything, either observation, radiation or chemotherapy with radiation. And chemo radiation can have very real and lasting side effects to the things we’ve spoken about. Speech swallowing, dry mouth, dental problems, etc. And this is dependent both on the radiation dose and the field size. Obviously, with the least risk of side effects being a dose of zero, otherwise known as not doing it. And so what- now, two trials we’ve done at UNC have done is to give what was optimal state-of-the-art systemic therapy, meaning medicines, anti-cancer medicines before the surgery. And then a transoral surgery in the first trial, the second one allowed any kind of surgery that was appropriate for the patient. And then a reassessment of that pathology report to try and see if we had enough reduction in the cancer from the anti-cancer medicines that we could either reduce the field size of the radiation or even eliminated entirely.
What you’re trying to do is save as much of the tongue as you possibly can to give people quality of life?
Weiss: Absolutely. But we’re trying to do it without compromising the cure rate, and perhaps even improving it through the use of that- of rapid initiation of the effective systemic therapy. If you’re going to do radiation, it can take weeks of planning. If you’re going to do surgery, you could wait a month for your O.R. time. If a decision is made to institute medicines, we can do that a week later. And so there is a nimbleness of this that we can get going and not let the cancer grow and in fact shrink it down before the definitive procedure is to come be that radiation or surgery.
Why is it called induction therapy?
Weiss: It’s historic. In most of the cancer world anything you do before your dominant attempt at cure, say before surgery in this case, is typically called neoadjuvant. Induction is a term mostly used in the leukemia world and not for solid tumors like tongue cancer. And its 30 year old history that really drove this. Actually much older than that, I was probably in a sandbox somewhere when that term was come up with. I have no idea why that term was used.
When you do this therapy, how quickly can you see a reduction in the tumor size and the cancer?
Weiss: In our neoadjuvant or induction trials, we’ve been shocked at how quickly we’ve seen reductions in some patients. Typically when you give chemotherapy or chemotherapy plus a targeted therapy, as in our first trial, or chemotherapy plus immunotherapy as in the second trial. Typically, you don’t assess the cancer until at least six weeks later with some of the more modern novel immunotherapies, even nine weeks or later, we were shocked that by Week 1 or 2 in some patients, people were already feeling better, starting to eat more, having less pain. We were really shocked that some of the patients had such dramatic early responses.
What is the treatment? How do you get the treatment?
Weiss: The treatment in the first trial, it was two IV chemotherapy drugs and one oral targeted therapy drug. And then the second trial, all the drugs were IV, two chemotherapy drugs plus an IV immune therapy drug.
How long was that? Is it like an hour IV treatment for three weeks, every day?
Weiss: It’s IV. Again, the regimens are all a little bit different, but about three hours IV. The schedule here is actually really important for some of the characteristics seen. And I’m talking about the schedule of the old school chemo, not even of the novel agents. Traditionally, chemotherapy is given as an atomic bomb of a dose, IV every three weeks. We all know the side effects and problems with that, including sometimes failure of efficacy. What we’ve learned in head and neck cancer is that if we instead divide out the dose and give a much lower dose weekly for six weeks in a row, some very desirable things happen. First, it’s less toxic. Second, if there are toxicities, instead of being stuck with three weeks of dose in the patient, we’re only stuck with one week of dose in, and so we can adjust what we’re doing. We can adjust supportive care meds, we can reduce dose, we can bail entirely much more nimbly than with the every three week dosing schedule. And the really delightful surprise is the response rate seems to go up not down with these weekly schedules.
Do you see this being a possibility for other cancer not just at the time?
Weiss: Yes, very much so. And actually, that’s already happening. There’s been a move across cancers to do a lot more upfront anti cancer, systemic therapy, AKA medicines before surgery. That is a theme that has already evolved quite substantially over time and in the era of immunotherapy has become even more attractive.
What’s next for this induction therapy and your clinical trials?
Weiss: The honest answer to the question is that the discussions on that have been on pause because we’ve been doing focused efforts on other things that we think are of greater promise for patients in development. Now obviously you probably don’t want that on film. But we’ve been working on our car and we’ve been working on some other stuff. We are using it in clinic. I mean it is used, but it isn’t standard of care. So give me a second, how to say this. We’ve only recently obtained mature data on the second of these clinical trials that combined chemotherapy with immunotherapy. And now we’re at a stage where we need to regroup. What’s happening in the clinic is that people are using this and related regimens outside of a clinical trial. It’s not entirely guidelines driven, it’s not entirely standard. But for cases that merit it, people are doing this. The second is that we need to take a step back, regroup, and ask, where should we go from here? And there are two major options that we will go once all these conversations are concluded. One option, as we did between trial 1 and trial 2, is that we can try to tweak the regimen and try to get to higher response rates and less toxicity. That’s really important. I’m not patient when it comes to my patients. I’m a recovering New Yorker, but beyond that, people are suffering. They need to be cured and they need to be cured with less toxicity now, if not yesterday. But there’s a problem. Once you get to good in the clinical world, it’s sometimes hard to get to better, because now you’ve set the bar much higher, and if you’re going to do a randomized trial against that, you might not be able to actually get to better. So there is a reason, in the interests of patients in the long term to sometimes be a little patient and tweak it. So one option is to tweak the regimen further in a third phase 2 trial. The other option is to try to go to phase 3 compared to standard of care. And the advantage of this is that you democratize it. If you have a winning phase 3, that becomes the guidelines endure standard of care and everyone across the country, if not the world can then get that with ease. The problem with that, as I said, Number 1, you’re not going to get to better, it becomes much harder. But Number 2, those are also massive, expensive, time consuming trials. And unlike a nimble phase 2 that we can simply do as an institution, these really require massive corporate backing to do.
Am I missing anything? Is there anything you want to add?
Weiss: I would just say that these are far from our only investigative efforts that are helping patients. We’ve been proud to be pioneers in the induction realm. We’ve been proud to be pioneers in the realm of intensification in HPV. And I would say that in head and neck right now, we are also pioneers in targeted immunotherapy, so neo antigen driven therapy. And I would highlight several efforts there. We are pleased to participate in an industry HPV vaccine study, therapeutic vaccination here. We have our own personalized cancer vaccine that has been seven years in development and is one sterility test moving to people. So very close after a lot of years of hard work. And we’re really excited to have IND and IRB approval for a car two study, cellular therapy for head and neck cancer. And that only lists a few of the many exciting things going on here.
Can you go ahead and tell me when you first met Mr. Bell?
Yarbrough: It’s been a few years back now. He came into the clinic with a pretty advanced tongue cancer, and we were trying to decide, basically, what was the best treatment for him. As we started exploring that, we were looking around for all the options, including standard therapy and some trials that were going on here at UNC.
Could you tell me about the huge tumor on his tongue?
Yarbrough: Mr. Bell had a pretty large tumor, the left side of his tongue that went past the midline into the tongue base. The thing about the head and neck area, even what people would consider small tumors, T1 for us are two centimeters. But if you think about a two centimeter area in your tongue and then if you have to do surgery, you need another two or one and half centimeters around that. So it gets big pretty quickly. His tumor, was the size of a tangerine on the left side of his tongue going past the midline.
Standard treatment would be pretty invasive and could be life-changing for him, correct?
Yarbrough: The standard treatment for oral cavity cancers is surgery first and then followed with radiation therapy or chemo radiation. For him, a tumor of that size would require a removal of most of his tongue. And the thing the tongue is important for, of course, people know about speech, but the other thing that it’s really important for is swallowing. So people with that amount of tongue that are missing likely will have trouble swallowing and could be G-tube dependent for the rest of their life.
Did you think Mr. Bell would be a good candidate for an induction therapy?
Yarbrough: Yes. To try to decrease the size of the tumor and improve his function after the treatment, we thought we may give him something called neoadjuvant therapy, which is a way of giving some chemotherapy, and in his case, some immune therapy before the surgery. It had a remarkable response for him, his tumor decreased in size markedly and really allowed us to do a fairly minimal resection of his tongue.
When you say “a reduce in size from a tangerine,” what size did it reduce to?
Yarbrough: I would say probably the size of a big marble.
Was this before or part of clinical trial?
Yarbrough: We were fortunate at that time to have a clinical trial going on that basically was set up to do this for surgical patients to give them therapy before surgery to try to decrease the amount of surgery they need. In Mr. Bell’s case, we’re really fortunate as well that we were also able to decrease his post operative therapy. Based on his pathology after tumor excision, he did not need aggressive post operative therapy. He basically ended up with a few more courses of immune therapy and was able to avoid radiation, which also has significant long term effects.
Mr. Bell seems like he can speak completely normal, eat completely normal. That’s pretty amazing.
Yarbrough: It’s just amazing what we’re able to do these days to help preserve people’s function. The first part is just bringing up viable tissue from eleshwere in the body and hooking it back up to blood vessels in the neck. We do that for all cancer patients now, but preserving the amount of tissue we’re able to preserve in him allowed him to speak, which I think is normally, and I think he’s on a regular diet and lives a normal life.
How long until you saw a difference in the size. How long did it take and how was it done? Was it done through an IV? Was it several treatments?
Yarbrough: For this trial, each course of therapy last usually about three weeks and you get a treatment every three weeks and you get several cycles before you’re reassessed. At the reassessment, then is time for the surgery. Then, after the surgery, there’s several more cycles of that therapy that last about a year.
How long until, during those cycles, did you start to see something change in Mr. Bell?
Yarbrough: Mr. Bell had a pretty robust response. Some patients, interestingly, their tumor seems to grow before it shrinks, and we think that’s immune cells infiltrating into the tumor that are eating the tumor, attacking the tumor. But because of that inflammatory response, the tumor can seem to grow a little bit before it shrinks down. So we try not to assess it too soon because the fear is we may do something that’s not necessary because the patient’s just starting to respond. So typically, and the trial demanded, we have a set time that we assess that tumor. Now obviously, if a tumor is growing through the therapy, we’re able to tell that and then we can go to surgery quicker.
In the clinical trial, were the responses overwhelming?
Yarbrough: We had several responses that were overwhelming like Mr. Bell’s and in fact, we had several patients who had complete pathologic responses, which means that when we went to surgery and removed the area where the tumor was, it felt like there was a tumor, but it was all scar tissue, all inflammatory tissue, and there was no tumor left for a lot of those patients.
Are there any adverse side effects?
Yarbrough: There are adverse side effects. Mr. Bell got standard, what we call cytotoxic chemotherapy in addition to immunotherapy. And with that, you can have things that people think about with chemotherapy, blood counts can drop, hair can thin, things like that. With the immune therapy, interestingly, there are side effects with that too. Your immune system if it gets overactive, then you can have autoimmune type diseases, which means your own body’s immune system can attack your thyroid or can attack your lungs. So we have to be very much on the lookout for those autoimmune type reactions. Now they can be reversed, so It’s not something that goes on the rest of your life, but those are side effects of the immune therapy.
What’s next for this?
Yarbrough: I think we’re really at just the start of this neoadjuvant therapy. And I think it’s going to become a standard of therapy for patients to try to decrease operative morbidity and decreased the intesity of post-operative therapy that is required. And the nice thing is part of this therapy is activating the patient’s own immune system to recognize and attack the tumor. And that means if there’s tumor cells somewhere else that we don’t know about in the neck, spread to the lung or somewhere else, their immune system is probably going after those cells in those other locations as well.
Anything we’re missing?
Yarbrough: No, I don’t think so. We’re just so happy that this is a new treatment paradigm that’s now getting more and more accepted. I think there’s still more trials to go on before we take this to standard of care, but I don’t think it’s going to be too long.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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